PURPOSE: To evaluate the classification, diagnosis, and natural course of ophthalmoplegia associated with mitochondrial disease. MATERIALS AND METHODS: Among 372 patients with mitochondrial disease who visited our hospital between January 2006 and January 2016, 21 patients with ophthalmoplegia were retrospectively identified. Inclusion criteria included onset before 20 years of age, pigmentary retinopathy, and cardiac involvement. The 16 patients who were finally included in the study were divided into three groups according to disease type: Kearns-Sayre syndrome (KSS), KSS-like, and chronic progressive external ophthalmoplegia (CPEO). RESULTS: The prevalences of clinical findings were as follows: ptosis and retinopathy, both over 80%; myopathy, including extraocular muscles, 75%; lactic acidosis, 71%; and elevated levels of serum creatine kinase, 47%. Half of the patients had normal magnetic resonance imaging findings. A biochemical enzyme assay revealed mitochondrial respiratory chain complex I defect as the most common (50%). The prevalence of abnormal muscle findings in light or electron microscopic examinations was 50% each, while that of large-scale mitochondrial DNA (mtDNA) deletions in a gene study was 25%. We compared the KSS and KSS-like groups with the CPEO patient group, which showed pigmentary retinopathy (p < 0.001), cardiac conduction disease (p=0.013), and large-scale mtDNA deletions (p=0.038). KSS and KSS-like groups also had gastrointestinal tract disorders such as abnormal gastrointestinal motility (p=0.013) unlike the CPEO group. CONCLUSION: Patients with KSS had gastrointestinal symptoms, which may indicate another aspect of systemic involvement. The presence of large-scale mtDNA deletions was an objective diagnostic factor for KSS and a gene study may be helpful for evaluating patients with KSS.
Acidosis, Lactic ; Classification ; Creatine Kinase ; Diagnosis ; DNA, Mitochondrial ; Electron Transport ; Enzyme Assays ; Gastrointestinal Motility ; Gastrointestinal Tract ; Genes, vif ; Humans ; Kearns-Sayre Syndrome ; Magnetic Resonance Imaging ; Mitochondrial Diseases* ; Muscles ; Muscular Diseases ; Ophthalmoplegia* ; Ophthalmoplegia, Chronic Progressive External ; Prevalence ; Retinitis Pigmentosa ; Retrospective Studies

Kearns-Sayre syndrome (KSS) is a rare multisystem mitochondrial disorder associated with progressive external ophthalmoplegia, atypical pigmentary degeneration of the retina, and complete heart block. KSS can lead to a risk of sudden death because of the potential progression of conduction abnormalities such as right or left bundle branch block or complete atrioventricular (AV) block. Here we describe the case of a KSS patient with type I diabetes who experienced syncope in the presence of complete AV block, confirmed by muscular biopsy.
Atrioventricular Block* ; Biopsy ; Bundle-Branch Block ; Death, Sudden ; Heart Block ; Humans ; Kearns-Sayre Syndrome* ; Mitochondrial Diseases ; Ophthalmoplegia, Chronic Progressive External ; Retina ; Syncope

BACKGROUNDKearns-Sayre syndrome (KSS) is a mitochondrial DNA (mtDNA) deletion disorder characterized by a triad of onset before 20 years of age, ophthalmoplegia, and pigmentary retinopathy. The heart and central nervous system are commonly involved. We summarized clinical and brain magnetic resonance imaging (MRI) features of a cohort of Chinese KSS patients.

METHODSNineteen patients confirmed by muscle biopsy and mtDNA analysis were enrolled. We examined clinical profiles, mainly focusing on changes in electrocardiogram (ECG) and brain MRI. The correlation between genotype and phenotype was statistically analyzed.

RESULTSThe mean age of onset was 9.6 ± 4.3 years, with all developing the classic triad at the time of diagnosis. Heart conduction block was detected in 63.2%, with four initially presenting as bundle branch block and developing into complete atrioventricular block over 3-72 months. Brain MRI showed symmetric high-T2 signals in 100% of cerebral and cerebellar white matter, as well as brainstem, 46.7% of basal ganglia, and 53.3% of thalamus. There were two patterns of cerebral white matter involvements, one with selective subcortical U-fibers and the other with periventricular white matter. The size of mtDNA deletion did not significantly correlate with age of onset or percentage of ragged blue fibers on muscle pathology.

CONCLUSIONSThe clinical features of KSS evolve dynamically, affecting the cardiac conduction system predominantly, highlighting the significance of ECG monitoring. Brain MRI showed changes involving both the white matter and deep gray nuclei. Clinical presentation or severity of muscle pathological changes is not related to the size of mtDNA deletions.

Adolescent ; Brain ; pathology ; physiology ; Child ; Child, Preschool ; DNA, Mitochondrial ; genetics ; Female ; Genotype ; Heart Block ; diagnosis ; genetics ; physiopathology ; Humans ; Kearns-Sayre Syndrome ; diagnosis ; genetics ; physiopathology ; Magnetic Resonance Imaging ; methods ; Male

Adolescent ; Humans ; Kearns-Sayre Syndrome ; surgery ; Male ; Nerve Block ; methods

Humans ; Kearns-Sayre Syndrome ; diagnosis ; genetics

Cognition ; physiology ; Disease Management ; Humans ; Kearns-Sayre Syndrome ; diagnosis ; physiopathology

Cognition ; physiology ; DNA, Mitochondrial ; genetics ; Genetic Testing ; Humans ; Kearns-Sayre Syndrome ; diagnosis ; genetics ; physiopathology ; Point Mutation ; genetics

Blepharoptosis is a common indication for surgery in plastic surgery units, yet its possible underlying pathology frequently remains unidentified. A 52-year-old man with a 20-year history of progressive bilateral ptosis (right>left) presented with recurrent ptosis of both eyes; he had undergone an operation on the levator aponeurosis 12 years prior. Due to the suspicion of an underlying disease, he was evaluated further. Chronic progressive external ophthalmoplegia in transition to the more severe syndromic variant Kearns-Sayre syndrome, a mitochondrial disorder causing myopathy, was diagnosed. The patient was treated with coenzyme Q10, and he underwent ptosis surgery on both eyes. This case illustrates a potentially multi-systemic disease that was diagnosed by a further evaluation of a common symptom, in this case worsening blepharoptosis. Awareness of myopathic symptoms is necessary to prevent overlooking serious yet improvable conditions.
Blepharoplasty ; Blepharoptosis* ; Humans ; Kearns-Sayre Syndrome* ; Middle Aged ; Mitochondrial Diseases ; Muscular Diseases ; Ophthalmoplegia, Chronic Progressive External ; Pathology ; Surgery, Plastic

Kearns-Sayre syndrome (KSS) is a rare mitochondrial myopathy that usually develops before 20 years of age. It demonstrates multisystemic involvement with a triad of cardinal features: progressive ophthalmoplegia, pigmentary retinopathy, and cardiac conduction abnormalities. In addition, patients might have cerebellar ataxia, a high content of protein in the cerebrospinal fluid, proximal myopathy, multiple endocrinopathies, and renal tubular acidosis. We herein report the successful obstetric analgesic and anesthetic management of a 28-year-old parturient patient with KSS who required labor analgesia and proceeded to deliver by cesarean section. We extrapolate that regional analgesia/anesthesia might be beneficial for reducing the metabolic demands associated with the stress and pain of labor in patients with KSS. Efficient postoperative analgesia should be provided to decrease oxygen requirements.
Acidosis, Renal Tubular ; Adult ; Analgesia ; Anesthesia, Obstetrical* ; Cerebellar Ataxia ; Cerebrospinal Fluid ; Cesarean Section ; Female ; Humans ; Kearns-Sayre Syndrome* ; Mitochondrial Myopathies ; Muscular Diseases ; Ophthalmoplegia ; Oxygen ; Pregnancy ; Retinitis Pigmentosa

Kearns-Sayre syndrome (KSS) is a rare mitochondrial myopathy that usually develops before 20 years of age. It demonstrates multisystemic involvement with a triad of cardinal features: progressive ophthalmoplegia, pigmentary retinopathy, and cardiac conduction abnormalities. In addition, patients might have cerebellar ataxia, a high content of protein in the cerebrospinal fluid, proximal myopathy, multiple endocrinopathies, and renal tubular acidosis. We herein report the successful obstetric analgesic and anesthetic management of a 28-year-old parturient patient with KSS who required labor analgesia and proceeded to deliver by cesarean section. We extrapolate that regional analgesia/anesthesia might be beneficial for reducing the metabolic demands associated with the stress and pain of labor in patients with KSS. Efficient postoperative analgesia should be provided to decrease oxygen requirements.
Acidosis, Renal Tubular ; Adult ; Analgesia ; Anesthesia, Obstetrical* ; Cerebellar Ataxia ; Cerebrospinal Fluid ; Cesarean Section ; Female ; Humans ; Kearns-Sayre Syndrome* ; Mitochondrial Myopathies ; Muscular Diseases ; Ophthalmoplegia ; Oxygen ; Pregnancy ; Retinitis Pigmentosa